Abstract 2179: Identification of ROS1 alterations in ctDNA from colorectal cancer patients in China

Abstract

Abstract Background: ROS proto-oncogene 1 (ROS1) is an oncogenic driver involved in various cancer types for which has FDA approved therapies. ROS1 has shown to undergo genetic rearrangements in a variety of human cancers including glioblastoma, non-small cell lung cancer (NSCLC), ovarian cancer, gastric adenocarcinoma and colorectal cancer. The rearrangements create fusion proteins in which the kinase domain of ROS1 becomes constitutively active and drives cellular proliferation. Although previous data have reported ROS1 fusions occur in 0.2% to 2.4% of colorectal cancers, the frequency and type of ROS1 alterations in Chinese CRC patients have not been fully reported. Methods: This study queried data from 1,083 colorectal cancer samples which underwent a targeted next-generation sequencing assay performed by 3DMed Clinical Laboratory Inc., a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory of 3D Medicines Inc. between January, 2017 and June, 2020 in China, to identify the incidence of ROS1 alterations detected in ctDNA in colorectal cancer patients. The detected genetic alteration types included single-nucleotide variants (SNVs), copy number variations (CNVs) and gene rearrangements/fusions. Results: ROS1 alterations were found in 114 patients among the 1,083 (10.5%) CRC patients' cohort, including 72 males and 42 females, median age was 58 years old. The ROS1 alterations included 110 (96.5%) SNVs, 3 (2.6%) CNVs and 1 (0.9%) GOPC-ROS1 fusion. Among the 110 single nucleotide variants, we identified 91 (82.7%) of ROS1 SNVs were nonsynonymous mutations. The top 5 co-occurring mutations in samples with ROS1 alterations were TP53 (71, 62.2%), CYP2C19 (48, 42.1%), APC (48, 42.1%), KRAS (46, 40.3%) and DPYD (42, 36.8%). Conclusion: Our study indicated that ctDNA can be used as a nonvasive methodology to detect cancer-specific genetic aberrations in plasma for CRC. ROS1 alterations occurred modestly in Chinese colorectal cancer patients. Co-occurring mutations may provide different biological subsets of patients with ROS1-mutant colorectal cancer to reveal patient outcomes and response to therapy. Further investigation could be focused on the effect of ROS1 nonsynonymous mutations on the ROS1 proteins in vitro to identify whether these are more actionable than currently recognized. Citation Format: Mojin Wang, Lili Zhu, Depei Huang, Xudong Shen, Hushan Zhang, Xueke She. Identification of ROS1 alterations in ctDNA from colorectal cancer patients in China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2179.